Tumor necrosis factor-alpha, microglia and astrocytes in AIDS dementia complex.

Abstract:

:The pathogenesis of HIV-associated cognitive changes is poorly understood. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) have been postulated to contribute to the mechanism of the neurological complications of HIV infection. One of the effects of TNF-alpha is to induce astrocyte proliferation in vitro. The purpose of this study was to look for a correlation between the expression of TNF-alpha, astrogliosis and the degree of cognitive impairment in 12 prospectively assessed AIDS cases without focal brain lesion, 8 of whom were demented. They were compared with 6 control patients without neurological disease. Neuropathological examination showed myelin pallor in 5 of the 8 demented patients. TNF-alpha expression was detected by immunohistochemistry in the midfrontal cortex, subcortical and deep white matter, and basal ganglia. Not only perivascular macrophages but also some microglial and endothelial cells were labeled. Most TNF-alpha-positive cells were in close contact with glial fibrillary acidic protein-positive astrocytes. They were more numerous than gp41-positive cells. Their density increased with increasing cognitive impairment and in parallel to the astrogliosis in the frontal cortex, basal ganglia and deep white matter. These findings further support the hypotheses that lesions of the deep white matter, driven by TNF-alpha, are associated with cognitive alteration, and that indirect effects of HIV infection in the brain participate in the development of HIV-associated dementia through a diffuse immune activation, mediated by cytokines.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Seilhean D,Kobayashi K,He Y,Uchihara T,Rosenblum O,Katlama C,Bricaire F,Duyckaerts C,Hauw JJ

doi

10.1007/s004010050646

subject

Has Abstract

pub_date

1997-05-01 00:00:00

pages

508-17

issue

5

eissn

0001-6322

issn

1432-0533

journal_volume

93

pub_type

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